Antithrombin III (ATryn, Thrombate III) Form

The following are antithrombin products requiring prior authorization: antithrombin III, human (Thrombate III®) and antithrombin, recombinant (ATryn®).
FDA Approved Indication(s) ATryn is indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients. Thrombate III is indicated in patients with hereditary antithrombin deficiency for: • Treatment and prevention of thromboembolism • Prevention of peri-operative and peri-partum thromboembolism
Limitation(s) of use: ATryn is not indicated for treatment of thromboembolic events in hereditary antithrombin deficient patients. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that ATryn and Thrombate III are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hereditary Antithrombin Deficiency (must meet all):

1. Diagnosis of hereditary antithrombin deficiency;
2. Prescribed by or in consultation with a hematologist;
3. Age ≥ 18 years;

4. Member meets one of the following (a or b): a. Request is for Thrombate III for the treatment or prevention of thromboembolism; b. Request is for prevention of peri-operative or peri-partum thromboembolism. Approval duration: 3 months (acute thrombosis or peri-operative/peri-partum prevention) or 6 months (prevention) B. Other diagnoses/indications (must meet 1 or 2):

   1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): Page 1 of 6

   CLINICAL POLICY Antithrombin III a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Hereditary Antithrombin Deficiency (must meet all):
   3. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

5. Member is responding positively to therapy. Approval duration: 3 months (acute thrombosis or peri-operative/peri-partum prevention) or 6 months (prevention) B. Other diagnoses/indications (must meet 1 or 2):

   1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      Page 2 of 6

   CLINICAL POLICY Antithrombin III III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents;
   B. Disseminated intravascular coagulation (DIC).
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DIC: disseminated intravascular coagulation FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable
   Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to goat and goat milk proteins (ATryn only) • Boxed warning(s): none reported Appendix D: General Information
   • In addition to the FDA-approved indications, antithrombin has been suggested for treatment of patients with DIC associated with trauma or sepsis. However, 2009 British guidelines for the diagnosis and management of DIC do not recommend antithrombin in patients with DIC without further prospective evidence in randomized controlled trials. More recent studies have not found clear benefit of antithrombin in treatment of DIC. A 2016 Cochrane review of antithrombin administration in critically ill patients concluded that there is insufficient evidence to support its use in any category of such patients, including those with sepsis and DIC. V. Dosage and Administration
   Drug Name Antithrombin III [human] (Thrombate III) Antithrombin [recombinant] (ATryn) Dosing Regimen Individualize dose to achieve antithrombin level of 80% to 120% of normal human plasma. Loading dose (IV infusion): 120% - baseline % x body weight (kg) / 1.4% Adjustment (as needed, IV infusion): Target % - trough % x body weight (kg) / 1.4% Maintenance: Loading dose x 0.6 IV every 24 hours as needed Treatment goal is to restore and maintain functional antithrombin activity levels between 80% - 120% (0.8 - 1.2 IU/mL) of
   normal. Maximum Dose Varies per baseline and target antithrombin levels Varies per baseline and target antithrombin levels Page 3 of 6

   CLINICAL POLICY Antithrombin III Drug Name Maximum Dose Dosing Regimen For surgical patients: Loading dose (IV infusion): 100% - baseline % x body weight (kg) / 2.3% Maintenance (IV infusion): 100% - baseline % x body weight (kg) / 10.2% For pregnant women: Loading dose (IV infusion): 100% - baseline % x body weight (kg) / 1.3% Maintenance (IV infusion): 100% - baseline % x body weight (kg) / 5.4% Continue administration of ATryn until adequate follow-on anticoagulation has been established. VI. Product Availability
   Drug Name Antithrombin III [human] (Thrombate III) Antithrombin [recombinant] (ATryn) Availability Single-dose vial: approximately 500 units Single-dose vial: approximately 525 IU or 1,750 IU VII.